Li Xiaofeng, Yin Guotao, Ji Wei, Liu Jianjing, Zhang Yufan, Wang Jian, Zhu Xiang, Zhu Lei, Dai Dong, Ma Wenchao, Xu Wengui
Department of Molecular Imaging and Nuclear Medicine, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, People's Republic of China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People's Republic of China.
Onco Targets Ther. 2020 Nov 13;13:11659-11668. doi: 10.2147/OTT.S271657. eCollection 2020.
To further improve the efficiency of adoptively transferred cytokine-induced killer (CIK) cell immunotherapy in breast cancer (BC), a reliable imaging method is required to visualize and monitor these transferred cells in vivo.
Herpes simplex virus 1-thymidine kinase () and 9-(4-[F]fluoro-3-(hydroxymethyl)butyl)guanine (F-FHBG) were used as a pair of reporter gene/reporter probe for positron emission tomography (PET) imaging in this study. Following the establishment of subcutaneous BC xenograft-bearing nude mice models, induced human CIK cells expressing reporter gene through lentiviral transduction were intravenously injected to nude mice. γ-radioimmunoassay was used to determine the specific uptake of F-FHBG by these genetically engineered CIK cells expressing in vitro, and F-FHBG micro positron emission tomography-computed tomography (PET-CT) imaging was performed to visualize these adoptively transferred CIK cells in tumor-bearing nude mice.
Specific uptake of F-FHBG by CIK cells expressing was clearly observed in vitro. Consistently, the localization of adoptively transferred CIK cells in tumor target could be effectively visualized by F-FHBG micro PET-CT reporter gene imaging.
PET-CT reporter gene imaging using F-FHBG as a reporter probe enables the visualization and monitoring of adoptively transferred CIK cells in vivo.
为进一步提高过继性转移细胞因子诱导的杀伤细胞（CIK）免疫疗法治疗乳腺癌（BC）的效率，需要一种可靠的成像方法在体内可视化并监测这些转移细胞。
在本研究中，单纯疱疹病毒1-胸苷激酶（）和9-(4-[F]氟-3-(羟甲基)丁基）鸟嘌呤（F-FHBG）被用作一对用于正电子发射断层扫描（PET）成像的报告基因/报告探针。在建立皮下荷人BC异种移植瘤裸鼠模型后，将通过慢病毒转导表达报告基因的诱导人CIK细胞静脉注射到裸鼠体内。采用γ放射免疫测定法测定这些体外表达的基因工程CIK细胞对F-FHBG的特异性摄取，并进行F-FHBG微型正电子发射断层扫描-计算机断层扫描（PET-CT）成像，以可视化荷瘤裸鼠体内这些过继性转移的CIK细胞。
体外可清楚观察到表达的CIK细胞对F-FHBG的特异性摄取。同样，通过F-FHBG微型PET-CT报告基因成像可有效可视化过继性转移的CIK细胞在肿瘤靶点的定位。
以F-FHBG作为报告探针的PET-CT报告基因成像能够在体内可视化并监测过继性转移的CIK细胞。
